The ultimate goal of this project is to understand the molecular events as cells migrate along a chemical gradient. Most of our studies utilize leukocytes and small formylmethionyl peptide attractants. Tyrosine appears to be an essential component of the cell surface receptor, and certain hydrophobic peptide esters inhibit agonist-receptor interaction. The events triggered by the interaction of peptide with a surface receptor include activation of both a membrane phospholipase and a protein methylesterase; these may contribute to chemotaxis by increasing membrane fluidity and inducing conformational changes in contractile proteins respectively. The cell may terminate its response to formylmethionyl peptides by oxidizing the methionyl sulfur of the attractant. Other regulatory systems under study include the antichemotactic effects of materials derived from tumors as well as glucocorticoids. Initial studies on fibroblast chemotaxis indicate that motility in this cell may involve processes similar to those in the leukocyte.